The overall objective of this project is to carry out molecular genetic investigations of the mechanisms of photoreceptor excitation and degeneration using Drosophila mutants, with the eventual goal of building a comprehensive picture of photoreceptor function in this organism. Among the specific experiments proposed are further characterizations of the norpA gene, completing the analysis of the brain-specific Go clone, and attempting to isolate eye-specific G protein clones. The heart of the proposal, however, is the drastically altered strategy for gene cloning which would more fully take advantage of the large number of ERG-defective mutants available in this lab. The new approach calls for mapping as many of the genes corresponding to the ERG-defective mutants as possible and, in parallel with mapping, isolating a pool of eye-specific genomic clones. The eye-specific clones that correspond to the mutant genes are to be identified by comparing chromosomal positions of eye-specific clones with those of mutant genes. The identification is then confirmed by various molecular techniques. In parallel with molecular characterization of the genes isolated by the above means, mutants with defects in the genes will be analyzed in detail. Because the phototransduction pathway in Drosophila is prototypical of one of the most widely utilized signal transduction cascades, the understanding of this pathway is likely to be of importance in understanding signal transduction in general. Moreover, insofar as many human disorders are thought to be due to errors in the components of this pathway, the proposed study is likely to contribute to the knowledge needed for eventual prevention and treatment of these disorders.